PROJECT SUMMARY/ ABSTRACT The increasing pace and international diffusion of developments in human genome editing research have prompted ongoing efforts to develop responsible governance for such research. One point of broad agreement across these efforts is that human genome editing research should prioritize medical applications over attempts to enhance human traits because of the moral concerns the latter would raise. What qualifies as human enhancement and how to address issues that may arise in this arena remain uncertain. Moreover, several influential reports expand their interpretation of medical applications beyond disease treatment to endorse disease prevention as a goal for genome editing research. Basic human genome research and animal studies aspiring to this goal are already underway. But preventing disease through human genome editing would incidentally facilitate human enhancement applications in a variety of ways. If these translational research efforts are penalized by policy concerns about those applications, then their preventive health benefits could be lost. Conversely, society could be caught off guard by the emergence of genome editing applications that evoke the very moral concerns that the policy line against enhancement is meant to forestall. To responsibly anticipate these challenges, science policymakers will need to know more about the salience of enhancement concerns in the context of preventive genome editing (PGE) research and how best to develop research governance to address them. This project addresses these needs through the following research questions: 1) How do the goals, incentives and values driving cases of preclinical PGE research affect the ways that its incidental enhancement implications are interpreted and addressed for governance purposes? 2) How well might different forms of research governance be expected to anticipate and address these different concerns? 3) Given the potential human health benefits of preventive genome editing research, what ethical weight should science policy give to the various enhancement concerns? Answering these questions requires both empirical research and ethical analysis. Aim 1 enlists scientists to examine the professional and social factors that shape the trajectory of basic research relevant to preventive genome editing. Their perspectives will inform a taxonomy of different ways of interpreting incidental enhancements for policy purposes, and preview of the governance challenges they will raise. Aim 2 follows national and global genome editing policy groups to capture the lessons of their experiences, in order to assess the relative merits of different approaches to governance in dealing with incidental enhancement concerns. Both of these efforts will be drawn together in Aim 3, to inform an empirically grounded ethical analysis of the policy choices facing those engaged in genome editing research governance in different cases. The product of this project will be a set of case studies designed to help science policy makers, the research community and the public anticipate the incidental enhancement concerns that preventive genome editing research will pose.